RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with trastuzumab and lapatinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin together with cyclophosphamide followed by paclitaxel, trastuzumab, and lapatinib works in treating patients with HER2/neu-overexpressed breast cancer.

The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate.

Determine the feasibility of dose-dense doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel, trastuzumab (Herceptin®), and lapatinib ditosylate in patients with HER2/neu-overexpressed/amplified breast cancer.

Secondary

Assess the toxicity of this regimen in these patients.

Determine the time to recurrence in patients treated with this regimen.

Determine the overall survival of patients treated with this regimen.

Explore the use of serial troponin I (cTnI) and C-reactive protein (CRP) as a predictor of cardiac toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients may receive therapy as neoadjuvant or adjuvant administration. Chemotherapy must be completed before breast surgery in case of neoadjuvant therapy. Adjuvant therapy must begin within 84 days after breast surgery.

Trastuzumab (Herceptin®) and lapatinib ditosylate: Beginning concurrently with paclitaxel, patients receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and then once every 3 weeks, beginning at least 1 week after completion of paclitaxel, for a total of 52 weeks. Patients also receive oral lapatinib ditosylate once daily, beginning concurrently with paclitaxel, for a total of 52 weeks.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, every 2 weeks during chemotherapy, and at 6, 9, and 18 months. Samples are examined for serial troponin and C-reactive protein.

After completion of study treatment, patients are followed every 3-6 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the breast

Bilateral synchronous breast tumors allowed

Any nodal status or tumor size allowed

No stage IV disease

HER2/neu-positive disease

3+ by IHC OR FISH-amplified

Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Male or female

Menopausal status not specified

ECOG performance status 0-1

Absolute neutrophil count ≥ 1,000/mm³

Platelet count ≥ 100,000/mm³

Bilirubin ≤ 1.1 mg/dL

SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective barrier contraception during and after completion of study therapy

LVEF ≥ 50% by MUGA scan

No peripheral neuropathy > grade 1

No active second malignancy within the past 5 years except for adequately treated nonmelanoma skin cancer or in situ carcinoma of the cervix

No known allergy or hypersensitivity to doxorubicin hydrochloride, cyclophosphamide, paclitaxel, or other drugs formulated in Cremophor EL

No psychiatric illness or concurrent medical conditions that would preclude study treatment

No other concurrent chemotherapy, radiotherapy, immunotherapy, or biotherapy for breast cancer

No concurrent drugs that may prolong the QT

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00482391